The present study aimed to explore the extent to which immunomodulators may protect against Klebsiella pneumonia lipopolysaccharide (K pn LPS) toxicity. Two immunomodulators (levamisole and DDB) were utilized in the present work. The study was carried out on male Sprague Dawley rats, and animals were divided into four groups: One group was injected with saline intraperitoneally (i.p.) and served as a control group. The other three groups were subcutaneously daily injected with repetitive doses of K pn LPS (10, 10, 20, 20 and 40 lg/kg, i.p., for 5 consecutive days). Two of these K pn LPS-injected groups were daily cotreated with either levamisole (3 mg/kg, for 5 consecutive days, p.o) or DDB (6 mg/kg, for 5 consecutive days, p.o). At the end of the experiment, the effects of the given treatment were evaluated as regarding relative spleen and thymus weights, certain hematological changes (total and differential white blood cells count (WBCs), red blood cells count (RBCs), platelet count (PLAT), hemoglobin content (Hb), bone marrow cell count, as well as the histopathological changes in each of the spleen, thymus and bone marrow. The obtained results revealed that K pn LPS induced body weight loss, splenomegaly, thymic atrophy, leukopenia and lymphocytopenia. Each of bone marrow cells count and reticulocytes and eosinophil percentages were noticeably decreased after 5 days of K pn LPS administration. Each of the utilized drugs potentiated LPS-induced lymphocytopenia and increased segmented cells. However, DDB coadministration prior to K pn LPS injection could prevent the drop in bone marrow nucleated cells count, total WBCs, reticulocytes count and eosinophils differential count restoring them to their normal ranges. The histopathological examination of thymus, spleen and bone marrow of rats treated with either of the two utilized immunomodulators confirmed the above-mentioned results. Finally, the study reveals that DDB co-administration exerts more pronounced modulatory effect on LPS-induced hematotoxicity.